CN111443135A - Method for determining concentrations of hydrochlorothiazide, losartan and losartan 5-carboxylate in plasma by liquid chromatography-mass spectrometry - Google Patents
Method for determining concentrations of hydrochlorothiazide, losartan and losartan 5-carboxylate in plasma by liquid chromatography-mass spectrometry Download PDFInfo
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- CN111443135A CN111443135A CN202010026639.2A CN202010026639A CN111443135A CN 111443135 A CN111443135 A CN 111443135A CN 202010026639 A CN202010026639 A CN 202010026639A CN 111443135 A CN111443135 A CN 111443135A
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Abstract
The invention provides a method for determining the concentration of hydrochlorothiazide, losartan and active hydroxy acid metabolite 5-losartan carboxylate in plasma by liquid chromatography-mass spectrometry, which comprises the following steps: (1) pre-treating a plasma sample; (2) detecting by adopting liquid chromatography-mass spectrometry; (3) preparing a standard curve; (4) measuring the concentrations of hydrochlorothiazide, losartan and active hydroxy acid metabolite 5-losartan carboxylate in plasma; the method of the invention is rapid, accurate, high in sensitivity and simple in operation, and serves for clinical application of medicines.
Description
Technical Field
The invention relates to the technical field of drug analysis, relates to an in vivo drug analysis and determination method, and particularly relates to a method for determining the concentration of hydrochlorothiazide, losartan and the active hydroxy acid metabolite 5-losartan carboxylate in blood plasma by liquid chromatography-mass spectrometry.
Background
Losartan Potassium hydrochlorothiazide tablets (L osartan Potasidum and HydrochlorothiazideTablets) are compound preparations containing losartan and hydrochlorothiazide, the losartan is an angiotensin II receptor antagonist, the hydrochlorothiazide is a diuretic, and the losartan Potassium hydrochlorothiazide tablets are used for reducing the risks of fatal or non-fatal cardiovascular diseases, primary stroke and myocardial infarction and reducing the stroke risks of patients with hypertension and left ventricular hypertrophy while treating hypertension.
Disclosure of Invention
The technical problem to be solved is as follows: in order to solve the problems, the invention provides a method for measuring the concentration of hydrochlorothiazide, losartan and losartan carboxylate, an active hydroxy acid metabolite of hydrochlorothiazide and losartan carboxylate in blood plasma.
The technical scheme is as follows: a method for determining the concentration of hydrochlorothiazide, losartan and losartan carboxylate, an active hydroxy acid metabolite of the hydrochlorothiazide and losartan, in plasma by liquid chromatography-mass spectrometry comprises the following steps:
(1) pretreatment of a plasma sample:
adding a formic acid solution into a plasma sample for acidification, adding an internal standard mixed solution, adding ethyl acetate for extraction, centrifuging at a high speed, absorbing supernatant, drying by blowing nitrogen, and adding an ACN solution to obtain a sample to be detected;
(2) detecting by adopting liquid chromatography-mass spectrometry:
① liquid chromatography determination, the conditions are that the chromatographic column is G L Sciences Inc., Inertsustatin AQ-C18HP,3 μm, 2.1 × 100 mM, the temperature of the chromatographic column is 40 ℃, the mobile phase A is an aqueous solution containing 5mM ammonium acetate and 0.05% acetic acid, the mobile phase B is a 100% ACN solution, the washing solution is a 50% ACN solution and a 100% ACN solution containing 0.1% trifluoroacetic acid, the temperature of the automatic sample feeding is 4 ℃, the flow rate is 0.4m L/min, the sample feeding amount is 5u L, and the analysis time is 3.5 min;
② mass spectrometry, the conditions are that the ion source is an electrospray ion source, the interface temperature is 300 ℃, the D L temperature is 250 ℃, the heating gas flow is 10.00L/min, the heating block temperature is 400 ℃, the drier flow is 10.00L/min, the anion mode detection, the scanning mode is multiple reaction monitoring, the ion reactions for quantitative analysis are m/z296.05 → m/269.15 which is hydrochlorothiazide, m/z421.15 → m/z157.25 which is losartan, and m/z435.15 → m/z157.15 which is 5-losartan carboxylate;
(3) preparation of a standard curve:
with EDTA-K2Diluting the working solution 20 times for anticoagulant plasma, collecting 150u L plasma sample, adding 50.0u L deuterium substituted internal standard mixed solution, mixing, adding 600u L ethyl acetate, and vortexingMixing for 10min, centrifuging at 4 deg.C for 10min at 2600g, collecting supernatant of 300 μ L, and separating with N2Drying, adding 150 mu L50% methanol for redissolving, shaking for 5min to obtain a standard curve sample, measuring standard samples with different concentrations by adopting the chromatographic and mass spectrum conditions, drawing a peak area-concentration standard curve to obtain a linear regression equation:
and (3) losartan: f (x) =2.09423 × x-0.00370339, R = 0.9984388;
hydrochlorothiazide: f (x) =1.88987 × x-0.00216372, R = 0.9989974;
5-losartan carboxylate: f (x) =2.94750 × x-0.00458261, R = 0.9993292;
(4) determination of the concentration of hydrochlorothiazide, losartan and their active hydroxy acid metabolites losartan 5-carboxylate in plasma:
preparing the plasma to be detected according to the sample preparation method in the step (1), detecting the sample to be detected according to the step (2) by adopting a liquid chromatography-mass spectrometry combined detection method, recording peak areas corresponding to the concentrations of hydrochlorothiazide, losartan and active hydroxy acid metabolites 5-losartan carboxylate, substituting the peak area ratios of the concentrations of hydrochlorothiazide, losartan and 5-losartan carboxylate thereof and an internal standard into the established standard curve, and calculating to obtain the concentrations of hydrochlorothiazide, losartan and 5-losartan carboxylate thereof in the plasma to be detected.
Preferably, in the step (1), the plasma sample is pretreated by taking EDTA-K2 as an anticoagulant and taking a deuterated compound of each analyte as an internal standard, adding 50.0u L of the internal standard mixed solution into 100u L of the plasma sample, adding 50.0 mu L1.0.0% of FA mixed solution, mixing, adding 600u L ethyl acetate, vortex mixing for 10min, centrifuging for 10min at 2600g at 4 ℃, taking 300 mu L supernatant, and taking N2And (4) drying, adding 150.0 mu L25% ACN for redissolving, and shaking uniformly for 5min to obtain a sample to be detected.
Has the advantages that: the method of the invention has the following advantages:
1. the pretreatment method is simple: after the plasma sample is acidified, the organic reagent is subjected to liquid-liquid extraction, and the method is suitable for conventional determination;
2. the method has strong specificity, namely adopting a G L Sciences Inc., Inertsustatin AQ-C18HP,3 mu m and 2.1 × 100 mM chromatographic column, taking a water phase (containing 5mM ammonium acetate and 0.05% acetic acid aqueous solution) and 100% ACN solution as a mobile phase, and performing gradient elution, wherein the retention time of hydrochlorothiazide is about 0.9min, the retention time of losartan is about 1.3min, and the retention time of 5-losartan carboxylate is about 1.8 min;
3. the sensitivity is high, and the lowest quantitative limit of the hydrochlorothiazide, the losartan and the 5-losartan carboxylate plasma is respectively 1.00, 2.00 and 4.00 ng/m L.
4. The method is rapid, accurate, high in sensitivity and simple to operate, and serves for clinical application of medicines.
Description of the drawings:
FIG. 1 shows ion chromatograms of hydrochlorothiazide, hydrochlorothiazide-13C 6, losartan-d 4, losartan 5-carboxylate and losartan 5-carboxylate-d 4;
FIG. 2 is a mass spectrum of human blank plasma;
FIG. 3 is a mass spectrum of human blank plasma after the addition of standard.
FIG. 4 is a diagram of the losartan linear regression equation;
FIG. 5 is a linear regression equation chart of losartan 5-carboxylate;
figure 6 is a linear regression equation for hydrochlorothiazide.
Detailed Description
The invention will be further elucidated with reference to specific embodiments, without being limited thereto, in conjunction with the accompanying drawings.
Examples
First, experimental material and instrument
Hydrochlorothiazide, losartan and metabolites thereof, namely 5-losartan carboxylate, and various deuterated internal standards, namely hydrochlorothiazide-13C 6, losartan-d 4 and losartan-d 4, are all provided by Canada TRC, acetonitrile, methanol, acetic acid, ammonium acetate, formic acid and the like are all in HP L C grade, and come from Fisher company in America, and other chemical reagents are analytically pure.
L CMS-8060 Mass spectrometer (Shimadzu corporation), L ab Solutions 6.84 SP1 data acquisition software (Shimadzu corporation, Mettler XS 105DU electronic balance (Mettler corporation, Switzerland), Eppendorf Centrifuge5424R high speed low temperature Centrifuge (Eppendorf corporation, Germany).
Second, the experimental procedure
1. Preparation of stock solution and working solution
Weighing a proper amount of hydrochlorothiazide, losartan and metabolites thereof, namely 5-losartan carboxylate, and various deuterated internal standards of hydrochlorothiazide-13C 6, losartan-d 4 and 5-losartan carboxylate-d 4, adding a certain amount of DMSO to prepare stock solutions with the content of 1.00mg/m L, respectively diluting the independent stock solutions in sequence by using 50% MeOH solution at room temperature to prepare working solutions of a standard curve sample and a quality control sample, and preparing all the working solutions in a transparent polypropylene tube and storing in a freezing refrigerator at-20 ℃.
2. Pretreatment of a plasma sample:
the plasma uses EDTA-K2 as anticoagulant, uses deuterated compounds of respective substances to be detected as internal standards, adds 50.0u L of internal standard mixed solution into 100u L of plasma sample, adds 50.0 mu L1.0.0% of FA mixed solution, adds 600u L ethyl acetate after mixing, vortex mixing for 10min, centrifuges for 10min at 2600g under 4 ℃, takes 300 mu L supernatant, and takes N2Drying, adding 150.0 mu L25% ACN for redissolving, and shaking for 5min to obtain a sample to be detected;
3. detecting by adopting liquid chromatography-mass spectrometry:
① liquid chromatography determination, the conditions are that the chromatographic column is G L Sciences Inc., Inertsustatin AQ-C18HP,3 μm, 2.1 × 100 mM, the temperature of the chromatographic column is 40 ℃, the mobile phase A is an aqueous solution containing 5mM ammonium acetate and 0.05% acetic acid, the mobile phase B is a 100% ACN solution, the washing solution is a 50% ACN solution and a 100% ACN solution containing 0.1% trifluoroacetic acid, the temperature of the automatic sample feeding is 4 ℃, the flow rate is 0.4m L/min, the sample feeding amount is 5u L, and the analysis time is 3.5 min;
② mass spectrometry, the conditions are that the ion source is an electrospray ion source, the interface temperature is 300 ℃, the D L temperature is 250 ℃, the heating gas flow is 10.00L/min, the heating block temperature is 400 ℃, the drier flow is 10.00L/min, the anion mode detection, the scanning mode is multiple reaction monitoring, the ion reactions for quantitative analysis are m/z296.05 → m/269.15 which is hydrochlorothiazide, m/z421.15 → m/z157.25 which is losartan, and m/z435.15 → m/z157.15 which is 5-losartan carboxylate;
4. preparation of a standard curve:
with EDTA-K2Diluting the working solution 20 times with plasma containing potassium as anticoagulant, collecting 150u L plasma sample, adding 50.0u L deuterium substituted internal standard mixed solution, mixing, adding 600u L ethyl acetate, vortex mixing for 10min, centrifuging at 4 deg.C for 10min at 2600g, collecting 300 μ L supernatant, and adding into N L2Drying, adding 150 mu L50% methanol for redissolving, shaking for 5min to obtain a standard curve sample, measuring standard samples with different concentrations by adopting the chromatographic and mass spectrum conditions, drawing a peak area-concentration standard curve to obtain a linear regression equation:
and (3) losartan: f (x) =2.09423 × x-0.00370339, R = 0.9984388;
hydrochlorothiazide: f (x) =1.88987 × x-0.00216372, R = 0.9989974;
5-losartan carboxylate: f (x) =2.94750 × x-0.00458261, R = 0.9993292;
5. determination of the concentration of hydrochlorothiazide, losartan and their active hydroxy acid metabolites losartan 5-carboxylate in plasma:
preparing the plasma to be detected according to the sample preparation method in the step (1), detecting the sample to be detected according to the step (2) by adopting a liquid chromatography-mass spectrometry combined detection method, recording peak areas corresponding to the concentrations of hydrochlorothiazide, losartan and active hydroxy acid metabolites 5-losartan carboxylate, substituting the peak area ratios of the concentrations of hydrochlorothiazide, losartan and 5-losartan carboxylate thereof and an internal standard into the established standard curve, and calculating to obtain the concentrations of hydrochlorothiazide, losartan and 5-losartan carboxylate thereof in the plasma to be detected.
Preferably, the plasma sample pretreatment in the step (1) is as follows.
Comparative example
Precision and accuracy of the method:
weighing a proper amount of hydrochlorothiazide, losartan and active hydroxy acid metabolite 5-losartan carboxylate, adding a certain amount of DMSO to prepare stock solutions with the content of 1.00mg/m L, respectively diluting the independent stock solutions in sequence by using 50% methanol solution at room temperature to prepare working solutions of quality control samples, and preparing all the working solutions in transparent polypropylene tubes and storing in a freezing refrigerator at-20 ℃.
Concentration of quality control working solution (ng/m L):
compound (I) | LLOQ QC | LQC | GMQC | MQC | HQC |
Losartan | 40.0 | 120 | 800 | 3200 | 8000 |
5-losartan carboxylate | 80.0 | 240 | 1600 | 6400 | 16000 |
Hydrochlorothiazide | 20.0 | 60.0 | 60.0 | 1600 | 4000 |
Precisely adding 100u L of a plasma sample into a 96-deep-well plate, adding 50.0u L of an internal standard mixed solution, adding 50.0 mu L.0% of FA mixed solution, mixing, adding 600u L ethyl acetate into a 96-deep-well plate, carrying out vortex mixing for 10min, centrifuging for 10min at 4 ℃ for 2600g, taking 300 mu L of supernatant into the 96-well plate, drying under N2, adding 150.0 mu L% of ACN for redissolving, shaking for 5min to obtain a quality control sample, measuring the quality control samples with different concentrations by adopting the chromatographic and mass spectrometry conditions to obtain peak areas of the hydrochlorothiazide, the losartan and active hydroxy acid metabolites 5-losartan thereof, substituting the peak areas into a peak area-concentration standard curve to obtain the actual concentration of the quality control sample (N = 3):
losartan | LLOQ QC | LQC | GMQC | MQC | HQC |
Theoretical concentration | 2.00 | 6.00 | 40.0 | 160 | 400 |
|
2.06 | 5.75 | 41.2 | 166 | 425 |
|
2.00 | 5.78 | 41.9 | 168 | 426 |
|
2.24 | 6.10 | 40.2 | 167 | 410 |
Mean value of | 2.10 | 5.88 | 41.1 | 167 | 420 |
RE% | 5.0 | -2.1 | 2.8 | 4.4 | 5.1 |
RSD% | 5.9 | 3.3 | 2.1 | 0.6 | 2.1 |
5-losartan carboxylate | LLOQ QC | LQC | GMQC | MQC | HQC |
Theoretical concentration | 4.00 | 12.0 | 80.0 | 320 | 800 |
|
4.14 | 12.0 | 80.0 | 331 | 840 |
|
4.32 | 12.1 | 81.9 | 325 | 831 |
|
4.14 | 12.6 | 82.5 | 325 | 843 |
Mean value of | 4.20 | 12.2 | 81.5 | 327 | 838 |
RE% | 5.0 | 1.9 | 1.8 | 2.2 | 4.8 |
RSD% | 2.5 | 2.6 | 1.6 | 1.1 | 0.7 |
Hydrochlorothiazide | LLOQ QC | LQC | GMQC | MQC | HQC |
Theoretical concentration | 1.00 | 3.00 | 20.0 | 80.0 | 200 |
|
1.03 | 2.89 | 20.2 | 79.4 | 208 |
|
1.02 | 2.87 | 20.0 | 79.1 | 208 |
|
1.06 | 2.98 | 19.5 | 80.2 | 208 |
Mean value of | 1.04 | 2.91 | 19.9 | 79.6 | 208 |
RE% | 3.7 | -2.9 | -0.5 | -0.5 | 4.0 |
RSD% | 2.0 | 2.0 | 0.7 | 0.7 | 0.0 |
From the data in the above table it can be seen that:
the experimental results of the method show that RE% is within 15% of acceptable range, and RSD% is within 15% of acceptable range. Therefore, the method has the advantages of good repeatability, high precision and accuracy, high sensitivity and low detection limit.
Claims (2)
1. A method for measuring the concentration of hydrochlorothiazide, losartan and losartan carboxylate, an active hydroxy acid metabolite of the hydrochlorothiazide and losartan, in plasma by liquid chromatography-mass spectrometry is characterized by comprising the following steps:
(1) pretreatment of a plasma sample:
adding a formic acid solution into a plasma sample for acidification, adding an internal standard mixed solution, adding ethyl acetate for extraction, centrifuging at a high speed, absorbing supernatant, drying by blowing nitrogen, and adding an ACN solution to obtain a sample to be detected;
detecting by adopting liquid chromatography-mass spectrometry:
① liquid chromatography determination, the conditions are that the chromatographic column is G L Sciences Inc., Inertsustatin AQ-C18HP,3 μm, 2.1 × 100 mM, the temperature of the chromatographic column is 40 ℃, the mobile phase A is an aqueous solution containing 5mM ammonium acetate and 0.05% acetic acid, the mobile phase B is a 100% ACN solution, the washing solution is a 50% ACN solution and a 100% ACN solution containing 0.1% trifluoroacetic acid, the temperature of the automatic sample feeding is 4 ℃, the flow rate is 0.4m L/min, the sample feeding amount is 5u L, and the analysis time is 3.5 min;
② mass spectrometry, the conditions are that the ion source is an electrospray ion source, the interface temperature is 300 ℃, the D L temperature is 250 ℃, the heating gas flow is 10.00L/min, the heating block temperature is 400 ℃, the drier flow is 10.00L/min, the anion mode detection, the scanning mode is multiple reaction monitoring, the ion reactions for quantitative analysis are m/z296.05 → m/269.15 which is hydrochlorothiazide, m/z421.15 → m/z157.25 which is losartan, and m/z435.15 → m/z157.15 which is 5-losartan carboxylate;
preparation of a standard curve:
with EDTA-K2Diluting the working solution 20 times for anticoagulant plasma, collecting 150u L plasma sample, adding 50.0u L deuterium substituted internal standard mixed solution, mixing, adding 600u L ethyl acetate, vortex mixing for 10min, centrifuging at 4 deg.C for 10min at 2600g, collecting 300 μ L supernatant, and adding N2Drying, adding 150 mu L50% methanol for redissolving, shaking for 5min to obtain standard curve samples, measuring standard samples with different concentrations by adopting the chromatographic and mass spectrum conditions, drawing a peak area-concentration standard curve to obtain a linear regression equation:
and (3) losartan: f (x) =2.09423 × x-0.00370339, R = 0.9984388;
hydrochlorothiazide: f (x) =1.88987 × x-0.00216372, R = 0.9989974;
losartan carboxylate: f (x) =2.94750 × x-0.00458261, R = 0.9993292;
(4) determination of the concentration of hydrochlorothiazide, losartan and their active hydroxy acid metabolites losartan 5-carboxylate in plasma:
preparing the plasma to be detected according to the sample preparation method in the step (1), detecting the sample to be detected according to the step (2) by adopting a liquid chromatography-mass spectrometry combined detection method, recording peak areas corresponding to the concentrations of hydrochlorothiazide, losartan and active hydroxy acid metabolites 5-losartan carboxylate, substituting the peak area ratios of the concentrations of hydrochlorothiazide, losartan and 5-losartan carboxylate thereof and an internal standard into the established standard curve, and calculating to obtain the concentrations of hydrochlorothiazide, losartan and 5-losartan carboxylate thereof in the plasma to be detected.
2. The method for determining the concentration of hydrochlorothiazide, losartan and their active hydroxy acid metabolites 5-losartan carboxylate in plasma by LC-MS in the step (1) is characterized in that the pretreatment of plasma samples in the step (1) is that EDTA-K2 is used as anticoagulant in plasma, deuterated compounds of respective analytes are used as internal standards, 50.0u L of internal standard mixed solution is added to 100u L of plasma samples, 50.0 mu L1.0.0% of FA mixed solution is added, 600u L ethyl acetate is added after mixing, vortex mixing is carried out for 10min, centrifugation is carried out for 10min at 2600g under the condition of 4 ℃, 300 mu L supernatant and N are taken, and N is used as active hydroxy acid metabolite2And (4) drying, adding 150.0 mu L25% ACN for redissolving, and shaking uniformly for 5min to obtain a sample to be detected.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111983052A (en) * | 2020-07-24 | 2020-11-24 | 合肥诺明药物安全研究有限公司 | Quantitative analysis method for blood concentration of HYR-PB21 effective component |
CN115902068A (en) * | 2022-12-30 | 2023-04-04 | 武汉大学人民医院(湖北省人民医院) | Method and device for detecting medicine components |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101609070A (en) * | 2008-06-16 | 2009-12-23 | 北京德众万全药物技术开发有限公司 | A kind of method of measuring related substances of losastan potassium/hydrochlorothiazide tablets with HPLC |
CN102558156A (en) * | 2012-02-24 | 2012-07-11 | 华东理工大学 | Preparation method of 5-losartan carbonate |
-
2020
- 2020-01-10 CN CN202010026639.2A patent/CN111443135A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101609070A (en) * | 2008-06-16 | 2009-12-23 | 北京德众万全药物技术开发有限公司 | A kind of method of measuring related substances of losastan potassium/hydrochlorothiazide tablets with HPLC |
CN102558156A (en) * | 2012-02-24 | 2012-07-11 | 华东理工大学 | Preparation method of 5-losartan carbonate |
Non-Patent Citations (6)
Title |
---|
DIPANJAN GOSWAMI ET AL.: "Pharmacokinetic Estimation Of Losartan, Losartan Carboxylic Acid And Hydrochlorothiazide In Human Plasma By LC/MS/MS Validated Method", 《CLINICAL RESEARCH AND REGULATORY AFFAIRS》 * |
RAMKUMAR DUBEY ET AL.: "Simultaneous Determination and Pharmacokinetic Study of Losartan, Losartan Carboxylic Acid, Ramipril, Ramiprilat, and Hydrochlorothiazide in Rat Plasma by a Liquid Chromatography/Tandem Mass Spectrometry Method", 《SCIENTIA PHARMACEUTICA》 * |
刘茜 等: "液相色谱串联质谱法测定人血浆中氯沙坦/氢氯噻嗪的浓度及其人体相对生物利用度研究", 《中国临床药理学杂志》 * |
曾欣 等: "HPLC-MS/MS法检测人血浆中氯沙坦、E-3174、氢氯噻嗪浓度及生物等效性评价", 《中南药学》 * |
林淑 等: "格列吡嗪和格列本脲对氯沙坦药动学的影响", 《中国现代应用药学》 * |
王蓉 等: "人体氢氯噻嗪血药浓度测定与药代动力学研究", 《中国药业》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111983052A (en) * | 2020-07-24 | 2020-11-24 | 合肥诺明药物安全研究有限公司 | Quantitative analysis method for blood concentration of HYR-PB21 effective component |
CN115902068A (en) * | 2022-12-30 | 2023-04-04 | 武汉大学人民医院(湖北省人民医院) | Method and device for detecting medicine components |
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